Human telomeres are tethered to the nuclear envelope during postmitotic nuclear assembly

Cell Rep. 2012 Dec 27;2(6):1521-9. doi: 10.1016/j.celrep.2012.11.019. Epub 2012 Dec 20.

Abstract

Telomeres are essential for nuclear organization in yeast and during meiosis in mice. Exploring telomere dynamics in living human cells by advanced time-lapse confocal microscopy allowed us to evaluate the spatial distribution of telomeres within the nuclear volume. We discovered an unambiguous enrichment of telomeres at the nuclear periphery during postmitotic nuclear assembly, whereas telomeres were localized more internally during the rest of the cell cycle. Telomere enrichment at the nuclear rim was mediated by physical tethering of telomeres to the nuclear envelope, most likely via specific interactions between the shelterin subunit RAP1 and the nuclear envelope protein Sun1. Genetic interference revealed a critical role in cell-cycle progression for Sun1 but no effect on telomere positioning for RAP1. Our results shed light on the dynamic relocalization of human telomeres during the cell cycle and suggest redundant pathways for tethering telomeres to the nuclear envelope.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • HeLa Cells
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Mitosis / physiology*
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism*

Substances

  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • SUN1 protein, human
  • TERF2IP protein, human
  • Telomere-Binding Proteins